Anti-Cancer, Anti-Microbial, Ciprofloxacin, Crystal Structure, Ruthenium(II), Ruthenium(II)–Arene
We thank the Science Foundation Ireland (Grant Nos. 11/RFP.1/CHS/3095 and 12/TIDA/B2384), the ERC (Grant No. 247450) and EPSRC (Grant No. EP/F042159/1) for their support for this work. We thank Professor Iztok Turel (University of Ljubljana, Slovenia) for the helpful discussions and also acknowledge COST CM1105 for being a platform to progress fruitful collaborations and for funding two highly valuable short-term scientific missions for ZU to conduct research in the laboratory of PJS.
7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics.
Chemistry | Medicinal-Pharmaceutical Chemistry | Medicine and Health Sciences
Ude Z, Romero-Canelón I, Twamley B, Fitzgerald Hughes D, Sadler PJ, Marmion CJ. A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity. Journal of Inorganic Biochemistry. 2016;160:210-217.
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